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Watsuki said that his editor wanted him to do "a big story," leading Watsuki to create Shishio. Therefore, according to Watsuki, Shishio had no model for his personality. Watsuki originally intended for Shishio to be motivated for revenge since it would make it easier for Watsuki to express Shishio's grief towards the government. However Watsuki believed that this would make the story "smaller in scale." Therefore Watsuki had Shishio motivated for revenge and a desire to conquer, therefore making him destructive in a manner similar to that of Serizawa Kamo of the Shinsengumi. Watsuki believes that some influence from Genjuro Kibagami of Samurai Shodown II (ShinSamurai Spirits) appeared in Shishio.

The visual model for Shishio is Aonuma Shizuma of Inugami Ke no Ichizoku ("The Inugami Family"); Watsuki saw this film as a child and took influences from it. When it was decided that Shishio would be burned on much of his body, Watsuki thought of a rubber mask similar to the one that Shizuma has. Watsuki decided against this idea since he felt it would be difficult to realistically convey rubber in black and white, he felt he could not portray "the sheer agony" of Shishio's condition, and it would be more difficult for Watsuki to draw Shishio's expressions. Ultimately Watsuki decided to have Shishio wear bandages. Since Watsuki felt having the character simply wrapped in bandages would not "be exciting," the bandages on Shishio's face became crisscrossed, making what Watsuki describes as "weird headgear," and otherwise "fancied" the design. Watsuki wanted Shishio to be "cool, like Kibagami," so Watsuki added a "sexy companion," a pipe, a folding screen, and an umbrella.[2]

Shishio's "Homura Dama" technique is original to the series, while the "Guren Kaina" is, in Watsuki's words, "pretty much a rip of "Daibaku Satsu," a move by the "Shura" Kagetsu Kazama character in Samurai Shodown IV (Samurai Spirits: Amakusa's Descent, TenSamu).[3]

In Volume 17 Watsuki stated that he thought, in retrospect, that Shishio was his version of "the appeal of evil." Watsuki explained that Shishio will not compromise his beliefs under any circumstances, has no objections to "using others as a means to an end," and seeks "absolute power" "with ruthless abandon." Watsuki explained that Shishio "is his own kind of ideal" and that he is an "anti-hero." Watsuki enjoyed drawing Shishio in his final fight with Kenshin. Watsuki felt that he could not draw the scene of Shishio's death as it appeared in his mind. Watsuki believes, "with some confidence," that the scene of Shishio in hell walking across a pile of skeletons is "as good a dramatization of a villain in RuroKen that we're ever going to get." Watsuki said that he would never write in a character like Shishio in all of the series he writes, but he planned to create a similar character in another series.[3]

In history police were forbidden from entering the Mount Hiei temple grounds, so criminals gathered there and claimed that they were there for "religious enlightenment." Because of this Watsuki located Shishio's hideout on Mount Hiei in Rurouni Kenshin.[4]

After the death of Yukishiro Tomoe, Himura Kenshin became a free wielding swordsman to protect members of the Ishin Shishi. Shishio Makoto, born August 1848 in Kyoto Prefecture,[1] became his successor as hitokiri (literally "manslayer", assassin) and was responsible for the assassination of I'izuka, the man who had betrayed the Choshu party. The future Meiji government was more secretive about Shishio than Kenshin; many members of the Chōshū and Satsuma clans (the members of the future Meiji government) had very little information on him.

Later, the new Meiji government believed it would be in their best interests to eliminate Shishio. While they had found Himura to be an idealistic servant of the Imperialist cause, Okubo and other Meiji officials correctly concluded that Shishio was an opportunistic sociopath who would undoubtedly use his vast knowledge of government secrets to plunge the country into turmoil for his own personal gain. Thus, during the Boshin War, Shishio was knocked out from a gunshot to the head, doused in oil and burned alive by the Ishin Shishi.[1] He survived, sustaining severe damage to his entire body to the point that he must wear bandages day and night to cover his disfigured skin, giving him an appearance similar to a mummy. It also limited the time he could fight. Any battle that surpassed fifteen minutes placed him in jeopardy of undergoing spontaneous combustion, as due to his lack of sweat glands he is unable to regulate his body temperatures.[1]

Shishio, with the aid from a man named Sadojima Hōji, assembled a group of the best fighters in Japan, called the Ten Swords (Juppongatana), to overthrow the Meiji government. He envisioned a Japan ruled by him, enforcing the principles of Social Darwinism through Anarchism and chaotic fighting. Using this belief, Shishio ran a campaign against the Meiji government, as he felt it was too weak to effectively lead the country. Using his motto, he molded an ideological disciple out of Seta Sōjirō, who served as his right-hand man, and the strongest of the Juppongatana. He planned to strengthen the economy with petroleum once he took over the country. At some point, he met Komagata Yumi, a former high-ranking geisha who despised the Meiji Government's new policies on prostitution, whom he shared a romantic relationship with.

Shishio is extremely ruthless and coldblooded. He lives by the belief that weak only exist for the benefit of the strong and generally appears devoid of compassion or mercy throughout the series.

However, he is not completely heartless. In spite of his sinister nature, he seems genuinely in love with Yumi whom he professed understood him as thoroughly as he understood her. He also possesses a dark sense of humor, claiming initially to Kenshin that he had enslaved an entire town so he could bathe in the hot springs with privacy. He was also able to form some bonds to a degree with Sōjirō and Hōji.

Shishio displays very high intelligence, in some ways giving him something of an evil genius persona. He is extremely crafty, being able to hide from the Meiji government despite their efforts to find him, and his plans nearly succeed in bringing them down. He also learns from his mistakes; after his brush with death from being knocked out with a bullet to the head, he takes to wearing a hachigane (iron headband) to keep that weakness from being exploited.

Shishio's sword, like Kenshin's, is a work by master swordsmith Arai Shakku: a blade called Mugenjin(無限刃,lit. "Unlimited Blade"?); its self-sharpening serrated edge flaked away in a regular pattern as it was used and it had become soaked in the flesh and body fat of the victims he had killed over the years. As a result he is able to execute fire-oriented techniques using the oils as fuel.

Shishio's monstrous strength, stamina, resistance to injury, and ability to read his opponent place him in at least the same league as Kenshin. (Shishio demonstrates the ability to stop Kenshin's Ryushosen using his fingers, dodge and counter Saito's Gatotsu Zeroshiki at point-blank range, see through Aoshi's Jisen-Kenbu technique, and take Sanosuke's Futae no Kiwami without any injuries or damage despite it making contact with his left cheek). Though it was stated that Shishio's previous knowledge of their abilities decreased the effectiveness of these techniques. In addition, he has the unique ability of being able to neutralize any technique he has seen before even once. (This explains how he was able to stop Kenshin's Ryushosen in their battle; he saw the technique when Kenshin used it against Senkaku in the Shingetsu village; and how he took Sanosuke's Futae no Kiwami to the face; he saw him use it to deflect the bullet from the gattling guns on his battleship during Sanosuke, Kenshin and Saito's combined assault on his battleship.)

Shishio uses Mugenjin to execute techniques referred to by Hōji as "The Three Secret Swords":

Ichi no Hiken: Homura Dama(壱の秘剣 焔霊,lit. "First Secret Sword: Burning Soul"?): This is the technique Shishio has used the most. Using friction to ignite the human fats that have soaked into his sword over time, this serves to distract the opponent from his swings. The result is being simultaneously burned and slashed,[1] more than compensating for the weakness of his serrated sword not being able to cut as deep as a normal one.

Ni no Hiken: Guren Kaina(弐の秘剣 紅蓮腕,lit. "Second Secret Sword: Crimson Lotus Arm"?): Shishio fills his gauntlets with gunpowder, and ignites them with the sparks caused by the Mugenjin. Thus it results in an explosion. Guren Kaina yields a lot of force and is usually performed while his opponent (such as Kenshin or Saitō Hajime) is at close range, preferably in his grip. It can backfire, however.

Tsui no Hiken: Kaguzuchi(終の秘剣 火産霊神,lit. "Final Secret Sword: Fire-Producing Spirit God"?): The Kaguzuchi is the ultimate technique in Shishio's arsenal. He activates it by scraping his blade from the base to the tip on the end of the scabbard, creating a miniature fire cyclone around the blade. The technique is not fully revealed, but it is believed[by whom?] that Shishio starts the fire and then slashes at the enemy, thus he can incinerate them entirely while still cutting them. Before Shishio could utilize the Kaguzuchi, he was countered by Kenshin's ultimate attack-Amakakeru Ryu no Hirameki. The Kaguzuchi is the name of the Shinto god of fire.

Note: In the Rurouni Kenshin: Enjou! Kyoto Rinne video game for the PlayStation 2, when Shishio makes contact with his Kaguzuchi, the flames rise upward and form a giant pillar or wall of flames, sending the opponent upward while severely burning him at the same time. Shishio then emerges from the flames as it dissipates. The opponent is seen falling behind him. In the game Jump Ultimate Stars, Shishio can perform the Kaguzuchi and it is listed as one of his support attacks.

For all of his power and skill, Shishio had a fatal weakness: Because he was set on fire, most of his sweat glands were burned. Therefore, once he engaged in battle, his body heat rose far above normal levels. Though Hōji believed Shishio's body heat contributed to his power in battle, it became his downfall, as he spontaneously combusted after 30 minutes in battle.

Kenshin and Saitō Hajime both spend a considerable amount of time looking for Shishio, meeting him once in Shingetsu Village. However, Shishio left soon after they found him. After the ordeal in Shingetsu village, Kenshin ventured onward to Kyoto where they would have their duel. Upon arriving in Kyoto, Kenshin searched for the swordsmith Arai Shakkū to forge a superior sakabatō. Shakkū died during the ten years that Kenshin had last seen him, and found his son Arai Seikū as head blacksmith instead. Kenshin instead sought after his former mentor Hiko Seijuro XIII, but discovered Seikū's predicament which involved one of the members of the Juppongatana (Ten Swords): Sawagejō Chō.

Meanwhile, Seta Sōjirō manages to convince Aoshi Shinomori to form an alliance with Shishio so the former could find Kenshin, while the latter could receive Aoshi's help to stop the Oniwabanshu and dig out Kenshin's location. Soon after, Shishio succeeds in reuniting the Juppongatana (save for Chō) and begins to proceed with his master plan.

After defeating and arresting Chō, he revealed that Shishio had planned to have the Ten Swords burn down Kyoto. However, Kenshin and Saitō find that the plan to burn down Kyoto was just a diversion, and the Shishio's real plan was to use a steel plated battleship, Rengoku ("Purgatory") that Hōji had purchased for him to attack Tokyo. Kenshin, Saitō, and Sagara Sanosuke pursue and intercept Shishio in a harbor not far from his target; And using a set of explosives Sanosuke obtained from his long-time friend, Tsukioka Tsunan, destroys the Rengoku. However Shishio, Sōjirō, Hōji and Yumi, escape.

Although his plan was foiled, Shishio was still not beaten, and instead arranged a duel to the death at Mount Hiei. Knowing that, Kenshin, Saitō, and Sanosuke travel there the next morning. While they were doing so, however, Shishio sent most of the Juppongantana out to kill Kenshin's friends at the Aoi-Ya, keeping only his strongest subordinates with him, and Shinomori Aoshi who had allied himself to Shishio in order to get to Kenshin. The members of the Ten Swords sent to the Aoi-Ya, however, were all defeated.

After defeating Aoshi and Sōjirō, Kenshin faced Shishio himself. Kenshin had been worn out and injured from his consecutive fights with Aoshi and Sōjirō, and Shishio knocked him out fairly easily. Saitō entered and ambushed Shishio, attempting kill with a blow to the head. However, Shishio's hachigane (a headband containing a metal plate to cover the temple) stopped the attack, after which he easily blocked every move Saitō used against him and defeated him. Sanosuke also entered to fight Shishio, but could not even injure Shishio, despite landing a direct Futae no Kiwami to the face. Finally, Aoshi entered, and managed to stall Shishio long enough for Kenshin to regain consciousness.

The two continued their fight, during which Shishio's body started to overheat to dangerous levels, but kept fighting despite that. At one point, Yumi intervened, standing in the way of a blow from Kenshin. Taking advantage of his moment of vulnerability, Shishio ran his sword through Yumi in an attempt to hit Kenshin. Kenshin ridiculed Shishio for betraying his love, but Shishio remarked that he understood that he did what Yumi wanted of him, which was in fact the case. Eventually, Shishio's body heat rose to the point where his blood evaporated and the fat and oils in his body ignited. The end result was Shishio combusting, and continued to burn until all that became of him was ash. He is later seen in Hell with Yumi and Hōji (who committed suicide in jail), commenting that they try and take it over.